Proteomic Profiling of Central Centrifugal Cicatricial Alopecia Reveals Role of Humoral Immune Response Pathway and Metabolic Dysregulation.

Proteomic profiling on other primary cicatricial alopecias, such as frontal fibrosing alopecia and lichen planopilaris, have suggested a T helper 1-mediated inflammatory pathway, but in central centrifugal cicatricial alopecia (CCCA), the protein expression patterns are unknown. In this study, we sought to characterize protein expression patterns in CCCA to identify biomarkers of disease activity that will identify potential therapeutic avenues for treatment. Scalp protein quantification was performed to understand protein expression patterns in affected versus unaffected scalps in CCCA. A total of 5444 proteins were identified, of which 148 proteins were found to be differentially expressed in CCCA-affected scalp, with upregulation of adaptive immune pathways (IGHG3, P = .034; IGHG4, P = .01; IGG1, P = .026) and markers of fibrosis (ITGA1, P = .016; SFRP2, P = .045; TPM2, P = .029; SLMAP, P = .016) and downregulation of metabolic proteins (ALOX15B, P = .003; FADS2, P = .006; ELOVL5, P = .007; FA2H, P = .017; FAR2, P = .011; SC5D, P < .001). Our analysis revealed, to our knowledge, previously unknown humoral immune canonical pathways, notably IgG, implicated in CCCA and additionally confirmed aberrant lipid metabolism pathways implicated in diabetes mellitus, suggesting unique mechanisms of disease in patients with CCCA.

Cosmetic injectables in skin of color: A review of uses, safety, and effectiveness of neuromodulators and dermal fillers.

BACKGROUND: Skin of color (SOC) individuals represent a growing market for cosmetic injectables and can have different aesthetic goals and responses to treatment. OBJECTIVE: A review of the uses, safety, and effectiveness of injectable neuromodulators and dermal fillers in SOC individuals. METHODS AND MATERIALS: A search of the PubMed/MEDLINE database was conducted from August 1960 to December 2020. Studies that were included either had a focus on SOC (>20% SOC study participants) or dedicated article content commenting on the safety and/or efficacy of injectables in SOC participants. RESULTS: Of the 503 publications identified, a total of 88 articles were selected for this review. Differences in aging and cultural factors can influence aesthetic goals amongst SOC populations. Available data suggests that botulinum toxin (BTX) and dermal fillers are safe and effective in SOC populations, with the largest amount of data existing for Asian populations. There remains a paucity of research on Black and Latinx populations. CONCLUSION: BTX and dermal fillers are generally effective and well tolerated in SOC populations, particularly Asian populations for which the greatest amount of data exists. More high quality, randomized controlled trials in Black and Latinx populations are warranted.

Artificial intelligence in dermatology: advancements and challenges in skin of color.

Artificial intelligence (AI) uses algorithms and large language models in computers to simulate human-like problem-solving and decision-making. AI programs have recently acquired widespread popularity in the field of dermatology through the application of online tools in the assessment, diagnosis, and treatment of skin conditions. A literature review was conducted using PubMed and Google Scholar analyzing recent literature (from the last 10 years through October 2023) to evaluate current AI programs in use for dermatologic purposes, identifying challenges in this technology when applied to skin of color (SOC), and proposing future steps to enhance the role of AI in dermatologic practice. Challenges surrounding AI and its application to SOC stem from the underrepresentation of SOC in datasets and issues with image quality and standardization. With these existing issues, current AI programs inevitably do worse at identifying lesions in SOC. Additionally, only 30% of the programs identified in this review had data reported on their use in dermatology, specifically in SOC. Significant development of these applications is required for the accurate depiction of darker skin tone images in datasets. More research is warranted in the future to better understand the efficacy of AI in aiding diagnosis and treatment options for SOC patients.

Optimisation of skin phototype classification.

Understanding individuals' skin pigmentation and photosensitivity is important in judging risk of skin cancer and response to certain treatment modalities. However, individuals with darkly pigmented skin are poorly represented in the widely used Fitzpatrick skin phototype (FST) system. Moreover, the FST system is prone to misuse, as it relies on subjective patient and clinician assessment of skin type, and does not clearly differentiate pigmentation from photosensitivity. By evaluating the key literature surrounding the FST system, its criticisms and proposed alternatives, this review serves to understand how skin phototype classification can be optimised.

Exogenous Ochronosis: Characterizing a Rare Disorder in Skin of Color.

Exogenous ochronosis is a rare dyschromia that primarily impacts those with skin of color. It is characterized by blue-black pigmentation and is associated with the long-term application of skin-lightening creams containing hydroquinone. Commonly confused with other dyschromias, the use of skin lightening topicals can cause paradoxical skin darkening in patients with known exogenous ochronosis. This is highly distressing to patients, often worsening the underlying dyschromia and making treatment more difficult. A 10-year retrospective analysis was conducted that revealed 25 patients with exogenous ochronosis. The average patient used a skin lightening cream for 9.2 years, with exogenous ochronosis most commonly arising on the cheeks (68%), forehead (24%), and temples (20%). Furthermore, this study identified that patients with exogenous ochronosis may respond well to treatment with Q-switched Alexandrite laser and microneedling. The incidence of exogenous ochronosis is likely to increase as demographics shift and access to a wide range of over-the-counter topicals becomes more available, both in the United States and worldwide. Therefore, it is imperative to better characterize exogenous ochronosis to identify best treatment practices for all patients.

Burden of Disease and Unmet Needs in the Diagnosis and Management of Atopic Dermatitis in Diverse Skin Types in Australia.

Atopic dermatitis (AD) is a common, chronic, inflammatory skin disease affecting Australians of all ages, races, ethnicities, and social classes. Significant physical, psychosocial, and financial burdens to both individuals and Australian communities have been demonstrated. This narrative review highlights knowledge gaps for AD in Australian skin of colour. We searched PubMed, Wiley Online Library, and Cochrane Library databases for review articles, systematic reviews, and cross-sectional and observational studies relating to AD in Australia for skin of colour and for different ethnicities. Statistical data from the Australian Institute of Health and Welfare and the Australian Bureau of Statistics was collected. In recent years, there has been substantially increased awareness of and research into skin infections, such as scabies and impetigo, among various Australian subpopulations. Many such infections disproportionately affect First Nations Peoples. However, data for AD itself in these groups are limited. There is also little written regarding AD in recent, racially diverse immigrants with skin of colour. Areas for future research include AD epidemiology and AD phenotypes for First Nations Peoples and AD trajectories for non-Caucasian immigrants. We also note the evident disparity in both the level of understanding and the management standards of AD between urban and remote communities in Australia. This discrepancy relates to a relative lack of healthcare resources in marginalised communities. First Nations Peoples in particular experience socioeconomic disadvantage, have worse health outcomes, and experience healthcare inequality in Australia. Barriers to effective AD management must be identified and responsibly addressed for socioeconomically disadvantaged and remote-living communities to achieve healthcare equity.

Disorders of Facial Hyperpigmentation.

Disorders of hyperpigmentation are common and challenging conditions which can arise due to a myriad of etiologic factors. Many of them can present across skin types but are more common in skin of color individuals with Fitzpatrick skin types III-VI. Facial hyperpigmentation, in particular, can have a significant impact on the quality of life of affected individuals due to its increased visibility. This article provides a comprehensive review of disorders of facial hyperpigmentation including epidemiology, pathogenesis, diagnostic considerations, and treatment approaches for these conditions.

Racial and Ethnic Disparities in Research and Clinical Trials.

Clinical trials are an essential component of research for determining the safety and efficacy of treatments for medical diseases. In order for the results of clinical trials to be generalizable to diverse populations, they must include participants at ratios that are reflective of national and global populations. A significant number of dermatology studies not only lack racial/ethnic diversity but also fail to report data on minority recruitment and enrollment. Reasons for this are multifold and are discussed in this review. Although steps have been implemented to improve this issue, greater efforts are needed for sustained and meaningful change.

Evaluation of Personalized Skincare Through in-silico Gene Interactive Networks and Cellular Responses to UVR and Oxidative Stress.

Purpose: Personalized approaches in dermatology are designed to match the specific requirements based on the individual genetic makeup. One major factor accounting for the differences in skin phenotypes is single nucleotide polymorphism (SNP) within several genes with diverse roles that extend beyond skin tone and pigmentation. Therefore, the cellular sensitivities to the environmental stress and damage linked to extrinsic aging could also underlie the individual characteristics of the skin and dictate the unique skin care requirements. This study aimed to identify the likely biomarkers and molecular signatures expressed in skin cells of different ethnic backgrounds, which could aid further the design of personalized skin products based on specific demands. Methods: Using data mining and in-silico modeling, the association of SNP-affected genes with three major skin types of European, Asian and African origin was analyzed and compared within the structure-function gene interaction networks. Cultured dermal fibroblasts were subsequently subjected to ultraviolet radiation and oxidative stress and analyzed for DNA damage and senescent markers. The protective applications of two cosmetic ingredients, Resveratrol and Quercetin, were validated in both cellular and in-silico models. Results: Each skin type was characterized by the presence of SNPs in the genes controlling facultative and constitutive pigmentation, which could also underlie the major differences in responses to photodamage, such as oxidative stress, inflammation, and barrier homeostasis. Skin-type-specific dermal fibroblasts cultured in-vitro demonstrated distinctive sensitivities to ultraviolet radiation and oxidative stress, which could be modulated further by the bioactive compounds with the predicted capacities to interact with some of the genes in the in-silico models. Conclusion: Evaluation of the SNP-affected gene networks and likely sensitivities of skin cells, defined as low threshold levels to extrinsic stress factors, can provide a valuable tool for the design and formulation of personalized skin products that match more accurately diverse ethnic backgrounds.

Variations in genetics, biology, and phenotype of cutaneous disorders in skin of color - Part I: Genetic, biologic, and structural differences in skin of color.

Skin of color (SOC) populations include those who identify as Black/African, Hispanic/Latinx, Asian/Pacific Islander, American Indian/Native Alaskan, Indigenous Australian, Middle Eastern, biracial/multiracial, or non-White; this list is far from exhaustive and may vary between and within cultures. Recent genetic and immunological studies have suggested that cutaneous inflammatory disorders (atopic dermatitis, psoriasis, and hidradenitis suppurativa) and malignancies (melanoma, basal cell carcinoma, and cutaneous T-cell lymphoma) may have variations in their immunophenotype among SOC. Additionally, there is growing recognition of the substantial role social determinants of health play in driving health inequalities in SOC communities. It is critically important to understand that social determinants of health often play a larger role than biologic or genetic factors attributed to "race" in health care outcomes. Herein, we describe the structural, genetic, and immunological variations and the potential implications of these variations in populations with SOC. This article underscores the importance of increasing the number of large, robust genetic studies of cutaneous disorders in SOC to create more targeted, effective therapies for this often underserved and understudied population. Part II of this CME will highlight the clinical differences in the phenotypic presentation of and the health disparities associated with the aforementioned cutaneous disorders in SOC.

Variations in genetics, biology, and phenotype of cutaneous disorders in skin of color. Part II: Differences in clinical presentation and disparities in cutaneous disorders in skin of color.

Skin of color (SOC) patients are projected to comprise the majority of the population by 2044, yet knowledge gaps in the clinical presentation and treatment of both common and uncommon dermatologic conditions in skin of color persist. Improved awareness of disparities that disproportionately impact SOC patients is necessary to address health inequity in the field of dermatology. The first part of this CME discussed structural, genetic, and immunophenotypic differences in SOC in common inflammatory disorders as well as cutaneous malignancies. The second part of this CME highlights clinical differences in the phenotypic presentation of the inflammatory disorders of atopic dermatitis, psoriasis, and hidradenitis suppurativa as well as the cutaneous malignancies of melanoma, basal cell carcinoma, and cutaneous T-cell lymphoma. Health disparities associated with each of these conditions are also discussed.